Expectations and outcomes of varying treatment strategies for CML presenting during pregnancy.

Diagnosing chronic myeloid leukaemia (CML) during pregnancy is rare. Tyrosine kinase inhibitors (TKIs) have traditionally been contraindicated owing to their teratogenicity. Management decisions should consider the risks to mother and foetus of uncontrolled disease and teratogenic medications. Further cases are required to build upon the paucity of current literature. We report 22 cases of CML diagnosed during pregnancy from 2002 to date. Twenty-one pregnancies resulted in healthy babies and one patient miscarried. Some patients remained untreated throughout pregnancy but the majority received one or both of interferon-α and leucapheresis. One patient was started on imatinib at Week 26, and one on hydroxycarbamide in the third trimester. We report haematological parameters during pregnancy to provide clinicians with realistic expectations of management. There were no fetal abnormalities related to treatment during pregnancy. Seventeen patients achieved at least major molecular response on first-line TKI. A diagnosis of CML during pregnancy can be managed without significant consequences for mother or child. Leucapheresis and interferon-α are generally safe throughout pregnancy. Despite having been avoided previously, there is growing evidence that certain TKIs may be used in particular circumstances during the later stages of pregnancy. Future work should aim to further elucidate this safety profile.

The effect of bariatric surgery type on cardiac reverse remodelling.

INTRODUCTION: Bariatric surgery is effective in reversing adverse cardiac remodelling in obesity. However, it is unclear whether the three commonly performed operations; Roux-en-Y Gastric Bypass (RYGB), Laparoscopic Sleeve Gastrectomy (LSG) and Laparoscopic Adjustable Gastric Band (LAGB) are equal in their ability to reverse remodelling. METHODS: Fifty-eight patients underwent CMR to assess left ventricular mass (LVM), LV mass:volume ratio (LVMVR) and LV eccentricity index (LVei) before and after bariatric surgery (26 RYGB, 22 LSG and 10 LAGB), including 46 with short-term (median 251-273 days) and 43 with longer-term (median 983-1027 days) follow-up. Abdominal visceral adipose tissue (VAT) and epicardial adipose tissue (EAT) were also assessed. RESULTS: All three procedures resulted in significant decreases in excess body weight (48-70%). Percentage change in VAT and EAT was significantly greater following RYGB and LSG compared to LAGB at both timepoints (VAT:RYGB -47% and -57%, LSG -47% and -54%, LAGB -31% and -25%; EAT:RYGB -13% and -14%, LSG -16% and -19%, LAGB -5% and -5%). Patients undergoing LAGB, whilst having reduced LVM (-1% and -4%), had a smaller decrease at both short (RYGB: -8%, p < 0.005; LSG: -11%, p < 0.0001) and long (RYGB: -12%, p = 0.009; LSG: -13%, p < 0.0001) term timepoints. There was a significant decrease in LVMVR at the long-term timepoint following both RYGB (-7%, p = 0.006) and LSG (-7%, p = 0.021), but not LAGB (-2%, p = 0.912). LVei appeared to decrease at the long-term timepoint in those undergoing RYGB (-3%, p = 0.063) and LSG (-4%, p = 0.015), but not in those undergoing LAGB (1%, p = 0.857). In all patients, the change in LVM correlated with change in VAT (r = 0.338, p = 0.0134), while the change in LVei correlated with change in EAT (r = 0.437, p = 0.001). CONCLUSIONS: RYGB and LSG appear to result in greater decreases in visceral adiposity, and greater reverse LV remodelling with larger reductions in LVM, concentric remodelling and pericardial restraint than LAGB.

Good mid- to long-term results of the cemented oxford phase 3 unicompartmental knee arthroplasty in a non-designer centre.

PURPOSE: Unicompartmental knee arthroplasty (UKA) provides patients with an alternative treatment to TKA in isolated medial compartment osteoarthritis providing better functional outcomes and faster recovery in the short term. Our aim was to quantify revision rates, predictors of revision, mortality rate and functionality of the Oxford Phase 3 UKA in a non-designer institution. METHODS: This was a retrospective review of prospectively collected regional registry data. All Oxford Phase 3 UKAs performed for medial tibio-femoral osteoarthritis of the knee joint were included from a single academic institution between the period of January 1st 2006 and December 30th 2009. Kaplan-Meier survivorship curves adjusting for loss to follow-up and deceased patients were generated. Primary outcome variables included all-cause and aseptic revision. Secondary outcome variables included functional outcome scores. Patients were reviewed at 6 months, 2 years, 5 years, 10 years and 15 years. RESULTS: A total of 64 cemented Oxford phase 3 UKAs were performed between January 2006 and November 2009. Fifteen-year follow-up data were available for 51 patients, of these 12 required revision. Survival rates, adjusting for patients that were either lost to follow-up or deceased, were 87.5% at 5 years, 81.4% at 10 years and 76.4% at 15 years. The overall aseptic revision rate at the time of review was 18.75% (n = 12). The only significant predictor of postoperative WOMAC score at 15 years was the preoperative WOMAC score (p = 0.03). CONCLUSION: The Oxford Phase 3 UKA for medial tibio-femoral arthritis has promising outcomes at 15-year follow-up with a survival rate of 76.4% in a non-designer centre. LEVEL OF EVIDENCE: III.

Treatment-related fertility impairment in long-term female childhood, adolescent and young adult cancer survivors: investigating dose-effect relationships in a European case-control study (PanCareLIFE).

STUDY QUESTION: Which chemotherapeutic agents and body site-specific radiation fields are dose-dependently associated with an increased risk of fertility impairment in long-term female childhood, adolescent and young adulthood (CAYA) cancer survivors? SUMMARY ANSWER: Busulfan, lower abdominal radiotherapy (RT) and total body irradiation (TBI) seem to be associated with fertility impairment at any dose, whereas gonadotoxicity of melphalan and procarbazine is suggested at medium/high (>140 mg/m2) or high dose (>5600 mg/m2) therapy, respectively. WHAT IS KNOWN ALREADY: Several treatment-related fertility deficits, as assessed by both self-reported outcomes and hormonal markers are known to occur following treatment of CAYA cancer. However, knowledge regarding precise dose-related estimates of these treatment-related risks are scarce. STUDY DESIGN, SIZE, DURATION: The current case-control study was nested within the PanCareLIFE cohort study. In total, 1332 CAYA survivors from 8 countries, 9 institutions and 11 cohorts, participated in and contributed data to the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: All participants were female 5-year CAYA cancer survivors. In total, 450 cases (fertility impaired survivors) and 882 matched controls (not fertility impaired survivors) were included. Fertility impairment was defined using both questionnaire data (primary or secondary amenorrhea; use of artificial reproductive techniques; unfulfilled wish to conceive) and hormonal data (FSH and anti-Müllerian hormone (AMH)). Multivariable logistic regression models were used to investigate the effect of (i) alkylating agent exposure, and (ii) dose categories for individual chemotherapeutic agents and for RT-exposed body sites. MAIN RESULTS AND THE ROLE OF CHANCE: A positive dose-effect relationship between cyclophosphamide equivalent dose (CED) score and fertility impairment was found, with survivors with a CED score > 7121 mg/m2 being at a significantly increased risk of fertility impairment (odds ratio (95% CI) = 2.6 (1.9-3.6) P < 0.001). Moreover, cumulative dose variables of the following treatments were significantly associated with fertility impairment: busulfan, carmustine, cyclophosphamide, melphalan, procarbazine, lower abdominal RT and TBI. Busulfan, lower abdominal RT and TBI seem to be associated with fertility impairment at any dose, whereas gonadotoxicity of melphalan and procarbazine is suggested at medium/high (>140 mg/m2) or high dose (>5600 mg/m2) therapy, respectively. LIMITATIONS, REASONS FOR CAUTION: Our study may have been subject to selection bias since data from about half of the original base cohorts were available for the current study. This could impact the generalizability of our study results. WIDER IMPLICATIONS OF THE FINDINGS: We identified survivors at high risk for fertility impairment and, consequently, for a reduced or even absent reproductive life span. Both girls and young women who are about to start anti-cancer treatment, as well as adult female survivors, should be counselled about future parenthood and referred to a reproductive specialist for fertility preservation, if desired. STUDY FUNDING/COMPETING INTEREST(S): This study has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602030. There are no competing interests. TRIAL REGISTRATION NUMBER: n/a.

Developing and testing a principle-based fidelity index for peer support in mental health services.

PURPOSE: Evidence suggests that the distinctive relational qualities of peer support-compared to clinical-patient relationships-can be eroded in regulated healthcare environments. Measurement of fidelity in trials of peer support is lacking. This paper reports the development and testing of a fidelity index for one-to-one peer support in mental health services, designed to assess fidelity to principles that characterise the distinctiveness of peer support. METHODS: A draft index was developed using expert panels of service user researchers and people doing peer support, informed by an evidence-based, peer support principles framework. Two rounds of testing took place in 24 mental health services providing peer support in a range of settings. Fidelity was assessed through interviews with peer workers, their supervisors and people receiving peer support. Responses were tested for spread and internal consistency, independently double rated for inter-rater reliability, with feedback from interviewees and service user researchers used to refine the index. RESULTS: A fidelity index for one-to-one peer support in mental health services was produced with good psychometric properties. Fidelity is assessed in four principle-based domains; building trusting relationships based on shared lived experience; reciprocity and mutuality; leadership, choice and control; building strengths and making connections to community. CONCLUSIONS: The index offers potential to improve the evidence base for peer support in mental health services, enabling future trials to assess fidelity of interventions to peer support principles, and service providers a means of ensuring that peer support retains its distinctive qualities as it is introduced into mental health services.

Lamellar to Micellar Phases and Beyond: When Tactic Active Systems Admit Free Energy Functionals.

We consider microscopic models of active particles whose velocities, rotational diffusivities, and tumbling rates depend on the gradient of a local field that is either externally imposed or depends on all particle positions. Despite the fundamental differences between active and passive dynamics at the microscopic scale, we show that a large class of such tactic active systems admit fluctuating hydrodynamics equivalent to those of interacting Brownian colloids in equilibrium. We exploit this mapping to show how taxis may lead to the lamellar and micellar phases observed for soft repulsive colloids. In the context of chemotaxis, we show how the competition between chemoattractant and chemorepellent may lead to a bona fide equilibrium liquid-gas phase separation in which a loss of thermodynamic stability of the fluid signals the onset of a chemotactic collapse.

Magnetite and Green Rust: Synthesis, Properties, and Environmental Applications of Mixed-Valent Iron Minerals.

Mixed-valent iron [Fe(II)-Fe(III)] minerals such as magnetite and green rust have received a significant amount of attention over recent decades, especially in the environmental sciences. These mineral phases are intrinsic and essential parts of biogeochemical cycling of metals and organic carbon and play an important role regarding the mobility, toxicity, and redox transformation of organic and inorganic pollutants. The formation pathways, mineral properties, and applications of magnetite and green rust are currently active areas of research in geochemistry, environmental mineralogy, geomicrobiology, material sciences, environmental engineering, and environmental remediation. These aspects ultimately dictate the reactivity of magnetite and green rust in the environment, which has important consequences for the application of these mineral phases, for example in remediation strategies. In this review we discuss the properties, occurrence, formation by biotic as well as abiotic pathways, characterization techniques, and environmental applications of magnetite and green rust in the environment. The aim is to present a detailed overview of the key aspects related to these mineral phases which can be used as an important resource for researchers working in a diverse range of fields dealing with mixed-valent iron minerals.

The value of non-invasive computed tomography coronary angiography in imaging patients with coronary artery bypass grafts.

INTRODUCTION: Invasive coronary angiography (ICA) is associated with higher complication rates in patients following coronary artery bypass surgery (CABG). CT coronary angiography (CTCA) has emerged as an attractive alternative. We assessed the impact of CTCA on subsequent ICA. METHODS: We identified 213 CABG patients undergoing CTCA between 2015 and 2018. In 151 the indication was suspected recurrence of angina. We then identified patients undergoing ICA within 1 year of CTCA. RESULTS: CTCA obviated the need for ICA in 115 cases (76%). CTCA was better at identifying targets for percutaneous coronary intervention (PCI) to saphenous vein grafts (SVG's) than to native vessels (89% vs 47%). 7 out of 10 lesions of "probable" significance by CTCA proved flow-limiting, and 4 out of 13 "indeterminate" lesions. CTCA concordance was 97% for left internal mammary (LIMA) grafts. CONCLUSION: CTCA directed management in a majority of patients without ICA. It identified a cohort of patients likely to be candidates for SVG PCI, but was less effective in identifying PCI targets in the native vessels. CTCA renders invasive LIMA cannulation redundant unless a target lesion is suspected.

'Everything was just getting worse and worse': deteriorating job quality as a driver of doctor emigration from Ireland.

BACKGROUND: Medicine is a high-status, high-skill occupation which has traditionally provided access to good quality jobs and relatively high salaries. In Ireland, historic underfunding combined with austerity-related cutbacks has negatively impacted job quality to the extent that hospital medical jobs have begun to resemble extreme jobs. Extreme jobs combine components of a good quality job-high pay, high job control, challenging demands, with those of a low-quality job-long working hours, heavy workloads. Deteriorating job quality and the normalisation of extreme working is driving doctor emigration from Ireland and deterring return. METHODS: Semi-structured qualitative interviews were conducted with 40 Irish emigrant doctors in Australia who had emigrated from Ireland since 2008. Interviews were held in July-August 2018. RESULTS: Respondents reflected on their experiences of working in the Irish health system, describing hospital workplaces that were understaffed, overstretched and within which extreme working had become normalised, particularly in relation to long working hours, fast working pace, doing more with less and fighting a climate of negativity. Drawing on Hirschman's work on exit, voice and loyalty (1970), the authors consider doctor emigration as exit and present respondent experiences of voice prior to emigration. Only 14/40 respondent emigrant doctors intend to return to work in Ireland. DISCUSSION: The deterioration in medical job quality and the normalisation of extreme working is a key driver of doctor emigration from Ireland, and deterring return. Irish trained hospital doctors emigrate to access good quality jobs in Australia and are increasingly likely to remain abroad once they have secured them. To improve doctor retention, health systems and employers must mitigate a gainst the emergence of extreme work in healthcare. Employee voice (about working conditions, about patient safety, etc.) should be encouraged and used to inform health system improvement and to mitigate exit.

What the public think about participation in medical research during an influenza pandemic: an international cross-sectional survey.

OBJECTIVES: The public and patients are primary contributors and beneficiaries of pandemic-relevant clinical research. However, their views on research participation during a pandemic have not been systematically studied. We aimed to understand public views regarding participation in clinical research during a hypothetical influenza pandemic. STUDY DESIGN: This is an international cross-sectional survey. METHODS: We surveyed the views of nationally representative samples of people in Belgium, Poland, Spain, Ireland, the United Kingdom, Canada, Australia and New Zealand, using a scenario-based instrument during the 2017 regional influenza season. Descriptive and regression analyses were conducted. RESULTS: Of the 6804 respondents, 5572 (81.8%) thought pandemic-relevant research was important, and 5089 (74.8%) thought 'special rules' should be applied to make this research feasible. The respondents indicated willingness to take part in lower risk (4715, 69.3%) and higher risk (3585, 52.7%) primary care and lower risk (4780, 70.3%) and higher risk (4113, 60.4%) intensive care unit (ICU) study scenarios. For primary care studies, most (3972, 58.4%) participants preferred standard enrolment procedures such as prospective written informed consent, but 2327 (34.2%) thought simplified procedures would be acceptable. For ICU studies, 2800 (41.2%) preferred deferred consent, and 2623 (38.6%) preferred prospective third-party consent. Greater knowledge about pandemics, trust in a health professional, trust in the government, therapeutic misconception and having had ICU experience as a patient or carer predicted increased willingness to participate in pandemic-relevant research. CONCLUSIONS: Our study indicates current public support for pandemic-relevant clinical research. Tailored information and initiatives to advance research literacy and maintain trust are required to support pandemic-relevant research participation and engagement.

Characterisation of the HLA-DRB1*07:01 biomarker for lapatinib-induced liver toxicity during treatment of early-stage breast cancer patients with lapatinib in combination with trastuzumab and/or taxanes.

HLA-DRB1*07:01 allele carriage was characterised as a risk biomarker for lapatinib-induced liver injury in a large global study evaluating lapatinib, alone and in combination with trastuzumab and taxanes, as adjuvant therapy for advanced breast cancer (adjuvant lapatinib and/or trastuzumab treatment optimisation). HLA-DRB1*07:01 carriage was associated with serum alanine aminotransferase (ALT) elevations in lapatinib-treated patients (odds ratio 6.5, P=3 × 10-26, n=4482) and the risk and severity of ALT elevation for lapatinib-treated patients was higher in homozygous than heterozygous HLA-DRB1*07:01 genotype carriers. A higher ALT case incidence plus weaker HLA association observed during concurrent administration of lapatinib and taxane suggested a subset of liver injury in this combination group that was HLA-DRB1*07:01 independent. Furthermore, the incidence of ALT elevation demonstrated an expected correlation with geographic HLA-DRB1*07:01 carriage frequency. Robust ALT elevation risk estimates for HLA-DRB1*07:01 may support causality discrimination and safety risk management during the use of lapatinib combination therapy for the treatment of metastatic breast cancer.

Enabling recruitment success in bariatric surgical trials: pilot phase of the By-Band-Sleeve study.

BACKGROUND: Randomized controlled trials (RCTs) involving surgical procedures are challenging for recruitment and infrequent in the specialty of bariatrics. The pilot phase of the By-Band-Sleeve study (gastric bypass versus gastric band versus sleeve gastrectomy) provided the opportunity for an investigation of recruitment using a qualitative research integrated in trials (QuinteT) recruitment intervention (QRI). PATIENTS/METHODS: The QRI investigated recruitment in two centers in the pilot phase comparing bypass and banding, through the analysis of 12 in-depth staff interviews, 84 audio recordings of patient consultations, 19 non-participant observations of consultations and patient screening data. QRI findings were developed into a plan of action and fed back to centers to improve information provision and recruitment organization. RESULTS: Recruitment proved to be extremely difficult with only two patients recruited during the first 2 months. The pivotal issue in Center A was that an effective and established clinical service could not easily adapt to the needs of the RCT. There was little scope to present RCT details or ensure efficient eligibility assessment, and recruiters struggled to convey equipoise. Following presentation of QRI findings, recruitment in Center A increased from 9% in the first 2 months (2/22) to 40% (26/65) in the 4 months thereafter. Center B, commencing recruitment 3 months after Center A, learnt from the emerging issues in Center A and set up a special clinic for trial recruitment. The trial successfully completed pilot recruitment and progressed to the main phase across 11 centers. CONCLUSIONS: The QRI identified key issues that enabled the integration of the trial into the clinical setting. This contributed to successful recruitment in the By-Band-Sleeve trial-currently the largest in bariatric practice-and offers opportunities to optimize recruitment in other trials in bariatrics.

Insights into Nitrate-Reducing Fe(II) Oxidation Mechanisms through Analysis of Cell-Mineral Associations, Cell Encrustation, and Mineralogy in the Chemolithoautotrophic Enrichment Culture KS.

Most described nitrate-reducing Fe(II)-oxidizing bacteria (NRFeOB) are mixotrophic and depend on organic cosubstrates for growth. Encrustation of cells in Fe(III) minerals has been observed for mixotrophic NRFeOB but not for autotrophic phototrophic and microaerophilic Fe(II) oxidizers. So far, little is known about cell-mineral associations in the few existing autotrophic NRFeOB. Here, we investigate whether the designated autotrophic Fe(II)-oxidizing strain (closely related to Gallionella and Sideroxydans) or the heterotrophic nitrate reducers that are present in the autotrophic nitrate-reducing Fe(II)-oxidizing enrichment culture KS form mineral crusts during Fe(II) oxidation under autotrophic and mixotrophic conditions. In the mixed culture, we found no significant encrustation of any of the cells both during autotrophic oxidation of 8 to 10 mM Fe(II) coupled to nitrate reduction and during cultivation under mixotrophic conditions with 8 to 10 mM Fe(II), 5 mM acetate, and 4 mM nitrate, where higher numbers of heterotrophic nitrate reducers were present. Two pure cultures of heterotrophic nitrate reducers (Nocardioides and Rhodanobacter) isolated from culture KS were analyzed under mixotrophic growth conditions. We found green rust formation, no cell encrustation, and only a few mineral particles on some cell surfaces with 5 mM Fe(II) and some encrustation with 10 mM Fe(II). Our findings suggest that enzymatic, autotrophic Fe(II) oxidation coupled to nitrate reduction forms poorly crystalline Fe(III) oxyhydroxides and proceeds without cellular encrustation while indirect Fe(II) oxidation via heterotrophic nitrate-reduction-derived nitrite can lead to green rust as an intermediate mineral and significant cell encrustation. The extent of encrustation caused by indirect Fe(II) oxidation by reactive nitrogen species depends on Fe(II) concentrations and is probably negligible under environmental conditions in most habitats.IMPORTANCE Most described nitrate-reducing Fe(II)-oxidizing bacteria (NRFeOB) are mixotrophic (their growth depends on organic cosubstrates) and can become encrusted in Fe(III) minerals. Encrustation is expected to be harmful and poses a threat to cells if it also occurs under environmentally relevant conditions. Nitrite produced during heterotrophic denitrification reacts with Fe(II) abiotically and is probably the reason for encrustation in mixotrophic NRFeOB. Little is known about cell-mineral associations in autotrophic NRFeOB such as the enrichment culture KS. Here, we show that no encrustation occurs in culture KS under autotrophic and mixotrophic conditions while heterotrophic nitrate-reducing isolates from culture KS become encrusted. These findings support the hypothesis that encrustation in mixotrophic cultures is caused by the abiotic reaction of Fe(II) with nitrite and provide evidence that Fe(II) oxidation in culture KS is enzymatic. Furthermore, we show that the extent of encrustation caused by indirect Fe(II) oxidation by reactive nitrogen species depends on Fe(II) concentrations and is probably negligible in most environmental habitats.

Adaptation of the By-Band randomized clinical trial to By-Band-Sleeve to include a new intervention and maintain relevance of the study to practice.

BACKGROUND: Recruitment into surgical RCTs can be threatened if new interventions available outside the trial compete with those being evaluated. Adapting the trial to include the new intervention may overcome this issue, yet this is not often done in surgery. This paper describes the challenges, rationale and methods for adapting an RCT to include a new intervention. METHODS: The By-Band study was designed in the UK in 2009-2010 to compare the effectiveness of laparoscopic adjustable gastric band and Roux-en-Y gastric bypass for severe obesity. It contained a pilot phase to establish whether recruitment was possible, and the grant proposal specified that an adaptation to include sleeve gastrectomy would be considered if practice changed and recruitment was successful. Information on changing obesity surgery practice, updated evidence and expert opinion about trial design were used to inform the adaptation. RESULTS: The pilot phase recruited over 13 months in 2013-2014 and randomized 80 patients (79 anticipated). During this time, major changes in obesity practice in the UK were observed, with gastric band reducing from 32·6 to 15·8 per cent and sleeve gastrectomy increasing from 9·0 to 28·1 per cent. The evidence base had not changed markedly. The British Obesity and Metabolic Surgery Society and study oversight committees supported an adaptation to include sleeve gastrectomy, and a proposal to do so was approved by the funder. CONCLUSION: Adaptation of a two-group surgical RCT can allow evaluation of a third procedure and maintain relevance of the RCT to practice. It also optimizes the use of existing trial infrastructure to answer an additional important research question. Registration number: ISRCTN00786323 (http://www.isrctn.com/).

Deficiencies in postgraduate training for healthcare professionals who provide diabetes education and support: results from the Diabetes Attitudes, Wishes and Needs (DAWN2) study.

AIMS: To consider the global provision of self-management diabetes education and training for healthcare professionals using data from the second Diabetes Attitudes, Wishes and Needs (DAWN2) study. METHODS: A total of 4785 healthcare professionals caring for people with diabetes were surveyed in 17 countries to assess diabetes healthcare provision, self-management support and training. RESULTS: Of the healthcare professionals surveyed, 33.5% received formal postgraduate training in self-management (19.3-51.4% across countries) and 62.9% received training for medical management of diabetes (47.6-70.6% variation). Training in psychological management was low (19.1%), ranging from 3.6 to 36.5%, while 20.4% (a range of 3.6-36.4% across countries) had received no postgraduate training. Overall, the greatest training need was in the management of psychological aspects of diabetes (59.5%). For some, training in a domain was positively associated with a perceived need for further training. Communication skills, for example, listening (76.9%) and encouraging questions (76.1%), were the skills most widely used. Discussion of emotional issues was limited; 31-60% of healthcare professionals across the different countries reported that this only occurred if initiated by patients. Approximately two-thirds of participants reported a need for major improvements in emotional/psychological support, but few had received training in this area, with consistent findings across professional affiliations. CONCLUSIONS: The present study shows that healthcare professionals report being insufficiently equipped to provide diabetes self-management education, including emotional and psychological aspects of diabetes, and many are not receiving postgraduate training in any part (including medical care) of the management of diabetes. It is paramount that those responsible for the continuing professional development of healthcare professionals address this skills gap.

Iron Isotope Fractionation during Fe(II) Oxidation Mediated by the Oxygen-Producing Marine Cyanobacterium Synechococcus PCC 7002.

In this study, we couple iron isotope analysis to microscopic and mineralogical investigation of iron speciation during circumneutral Fe(II) oxidation and Fe(III) precipitation with photosynthetically produced oxygen. In the presence of the cyanobacterium Synechococcus PCC 7002, aqueous Fe(II) (Fe(II)aq) is oxidized and precipitated as amorphous Fe(III) oxyhydroxide minerals (iron precipitates, Feppt), with distinct isotopic fractionation (ε56Fe) values determined from fitting the δ56Fe(II)aq (1.79‰ and 2.15‰) and the δ56Feppt (2.44‰ and 2.98‰) data trends from two replicate experiments. Additional Fe(II) and Fe(III) phases were detected using microscopy and chemical extractions and likely represent Fe(II) and Fe(III) sorbed to minerals and cells. The iron desorbed with sodium acetate (FeNaAc) yielded heavier δ56Fe compositions than Fe(II)aq. Modeling of the fractionation during Fe(III) sorption to cells and Fe(II) sorption to Feppt, combined with equilibration of sorbed iron and with Fe(II)aq using published fractionation factors, is consistent with our resulting δ56FeNaAc. The δ56Feppt data trend is inconsistent with complete equilibrium exchange with Fe(II)aq. Because of this and our detection of microbially excreted organics (e.g., exopolysaccharides) coating Feppt in our microscopic analysis, we suggest that electron and atom exchange is partially suppressed in this system by biologically produced organics. These results indicate that cyanobacteria influence the fate and composition of iron in sunlit environments via their role in Fe(II) oxidation through O2 production, the capacity of their cell surfaces to sorb iron, and the interaction of secreted organics with Fe(III) minerals.

Precision Measurement of the Radiative ß Decay of the Free Neutron.

The standard model predicts that, in addition to a proton, an electron, and an antineutrino, a continuous spectrum of photons is emitted in the ß decay of the free neutron. We report on the RDK II experiment which measured the photon spectrum using two different detector arrays. An annular array of bismuth germanium oxide scintillators detected photons from 14 to 782 keV. The spectral shape was consistent with theory, and we determined a branching ratio of 0.00335±0.00005[stat]±0.00015[syst]. A second detector array of large area avalanche photodiodes directly detected photons from 0.4 to 14 keV. For this array, the spectral shape was consistent with theory, and the branching ratio was determined to be 0.00582±0.00023[stat]±0.00062[syst]. We report the first precision test of the shape of the photon energy spectrum from neutron radiative decay and a substantially improved determination of the branching ratio over a broad range of photon energies.

Guidelines for timely initiation of chemotherapy: a proposed framework for access to medical oncology and haematology cancer clinics and chemotherapy services.

These guidelines, informed by the best available evidence and consensus expert opinion, provide a framework to guide the timely initiation of chemotherapy for treating cancer. They sit at the intersection of patient experience, state-of-the-art disease management and rational efficient service provision for these patients at a system level. Internationally, cancer waiting times are routinely measured and publicly reported. In Australia, there are existing policies and guidelines relating to the timeliness of cancer care for surgery and radiation therapy; however, until now, equivalent guidance for chemotherapy was lacking. Timeliness of care should be informed, where available, by evidence for improved patient outcomes. Independent of this, it should be recognised that shorter waiting periods are likely to reduce patient anxiety. While these guidelines were developed as part of a proposed framework for consideration by the Victorian Department of Health, they are clinically relevant to national and international cancer services. They are intended to be used by clinical and administrative staff within cancer services. Adoption of these guidelines, which are for the timely triage, review and treatment of cancer patients receiving systemic chemotherapy, aims to ensure that patients receive care within a timeframe that will maximise health outcomes, and that access to care is consistent and equitable across cancer services. Local monitoring of performance against this guideline will enable cancer service providers to manage proactively future service demand.

A survey of manufacturing and handling practices for monoclonal antibodies by pharmacy, nursing and medical personnel.

INTRODUCTION: There is a paucity of data available to assess the occupational health and safety risk associated with exposure to monoclonal antibodies. Industry standards and published guidelines are conflicting or outdated. Guidelines offer contrary recommendations based on an array of methodological approaches. This survey aimed to describe current practices, beliefs and attitudes relating to the handling of monoclonal antibodies by Australian medical, nursing and pharmacy clinicians. METHODS: An electronic survey was distributed between June and September 2013. Respondents were surveyed on three focus areas: institutional guideline availability and content, current practices and attitudes. Demographic data relating to respondent and primary place of practice were also collected. RESULTS: A total of 222 clinicians completed the survey, with representation from all targeted professional groups and from a variety of geographic locations. 92% of respondents reported that their institution prepared or administered monoclonal antibodies, with 87% specifically handling anti-cancer monoclonal antibodies. Monoclonal antibodies were mostly prepared onsite (84-90%) and mostly within pharmacy clean-rooms (75%) and using cytotoxic cabinets (61%). 43% of respondents reported access to institutional monoclonal antibody handling guidelines with risk reduction strategies including training and education (71%), spill and waste management (71%), procedures for transportation (57%) and restricted handling (50%). Nurses had a stronger preference towards pharmacy manufacturing than both doctors and pharmacists for a range of clinical scenarios. 95% of all respondents identified that professional or regulatory body guidelines are an important resource when considering handling practices. CONCLUSION: Monoclonal antibodies are most commonly handled according to cytotoxic drug standards and often in the absence of formal guidelines.

Use of Selected Scavengers for the Determination of NF-TiO2 Reactive Oxygen Species during the Degradation of Microcystin-LR under Visible Light Irradiation.

Although UV-induced TiO2 photocatalysis involves the generation of several reactive oxygen species (ROS), the formation of hydroxyl radicals are generally associated with the degradation of persistent organic contaminants in water. In this study, a variety of radical scavengers were employed to discriminate the roles of different ROS during visible light activated (VLA) photocatalysis using nitrogen and fluorine doped TiO2 (NF-TiO2) in the degradation of the hepatotoxin, microcystin-LR (MC-LR) in water. The addition of hydroxyl radical scavengers, methanol and tert-butyl alcohol to the reaction mixture resulted in negligible inhibition of VLA NF-TiO2 photocatalytic degradation of MCLR at pH 3.0 and only partial inhibition at pH 5.7. While hydroxyl radicals generally play the primary role in UV TiO2 photocatalysis, the minimal influence of MeOH and t-BuOH on the degradation process under these experimental conditions indicates hydroxyl radicals (•OH) do not play the primary role in VLA NF-TiO2 photocatalysis. However, strong inhibition was observed in VLA NF-TiO2 photocatalytic degradation of MC-LR in the presence of superoxide dismutase, benzoquinone and catalase at pH 3.0 and 5.7 indicating O2•- and H2O2 play critical roles in the degradation process. Similar degradation rates were observed in the presence of singlet oxygen scavenger, deuterium oxide, which enhances singlet oxygen mediated processes further suggesting singlet oxygen does not play a key role in the degradation of MCLR in these system. Formic acid and cupric nitrate were added to probe the roles of the valence band holes and conduction band electrons, respectively. Under UV+vis light irradiation, almost complete inhibition of MC-LR removal is observed with NF-TiO2 in the presence of •OH scavengers at pH 5.7. These results demonstrate that solution pH plays a major role in the formation and reactivities of ROS during VLA NF-TiO2 photocatalysis. The adsorption strength of the scavengers and MCLR onto NF-TiO2 as well as the speciation of the ROS as a function of pH need to be carefully considered since they also play a key role in the efficiency of the process. These results indicate the reduction of molecular oxygen by photo-generated electrons rather than hydroxyl radicals produced by oxidative reactions of photo-generated holes play a key role in the of VLA NF-TiO2 photocatalytic degradation of MC-LR.